PURPOSE OF REVIEW: The treatment landscape in advanced and metastatic renal cell carcinoma (RCC) is moving from the inhibition of tyrosine kinases (TKI) and the mammalian target of rapamycin (mTOR) inhibitors to specific immunooncology agents like immune checkpoint inhibitors (ICI). The review focus on the recent immunooncology developments and available trial results within the last 12 months. RECENT FINDINGS: ICI as monotherapy (nivolumab) or immunooncology and immunooncology combinations (nivolumab and ipilimumab) demonstrated positive results on prolonged overall survival in phase III trials...

With recent advances in immunooncology and the introduction of checkpoint inhibitors into clinical practice for many cancers, the treatment landscape of urothelial carcinoma has changed dramatically and will continue to change further. Currently, a number of compounds and combinations are under investigation in numerous clinical trials and various clinical scenarios for bladder cancer. Areas covered: In this review, the authors provide an overview of the history and rationale for immunotherapy in bladder cancer...

Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment...

Oncoimmunology (or immunooncology) is a burgeoning specialty of precision ("personalized") medicine designed to heighten the antitumor response of the immune system against molecules expressed excessively or only by tumor cells. This focus is necessary, as cancers are polyclonal tissues comprised of antigenically heterogeneous cells, the exact composition of which is shaped by the balance between antitumor immunity and tumor-promoting inflammation. Key targets include enhancing immune system (especially T cell) reactivity, inhibiting immune checkpoints, and promoting tumor cytolysis...

Data published in November 2016 showed a significant survival benefit for the PD-1 antibody Pembrolizumab in the second-line treatment of metastatic urothelial cancer in comparison to standard chemotherapy. Other PD-1/PD-L1 antibodies are being tested in advanced clinical trials. This class of substances will become standard of care from the time of their approval which is expected for 2017 and will replace vinflunine, which is currently recommended in the German guideline. PD-1/PD-L1 directed substances are also being tested as a first line treatment of metastatic urothelial carcinoma...

Cancer immunotherapy is coming of age, as outstanding results can be achieved in the therapy of cancer with poor prognosis by altering the patients' immune system and by promoting the immune response against tumours. Amongst immunotherapies, the immune checkpoint inhibitors (ICI) proved to be the most effective, primarily in the treatment of solid tumours, including melanoma, non-small cell lung carcinoma, and classical Hodgkin's lymphoma. The reason for this efficacy is the immunosuppressive microenvironment typical for many cancer types, directly and indirectly inhibiting effector T-cell responses...

Metastatic urothelial carcinoma of the bladder is an aggressive malignancy with poor prognosis, reflecting a lack of effective systemic therapies. The current standard of care includes multiagent platinum-based chemotherapy; however a majority of patients do not respond to treatment and most eventually succumb to disease. Recently, renewed interest in immunotherapy in the form of immune-checkpoint inhibition has gained widespread attention for a number of malignancies. Atezolizumab, an anti-PDL1 antibody, has been shown to be effective in a subset of patients previously treated with or unfit for platinum-based chemotherapy, and has shown durable responses with a good tolerability profile...

Immunooncology (IO) is the buzz word today and it has everyone doing IO research. If we look back at the history of cancer treatment, the survival rate was measured in months which, according to oncologists, was a lot back then because the mortality rate in most cancers was 100%. However, most traditional chemotherapies were not well tolerated because they would kill both cancerous and healthy cells, which lead to major side effects such as loss of hair, nausea and vomiting, and risk of infection. Survival was better but not much better depending on the type of cancer and the patient's own genetic and physiological make-up...

Immune checkpoint inhibitors are establishing itselves as a new systemic treatment option (in addition to chemotherapy and targeted therapy) for metastatic tumours. (Re)activating the immune system, these antibodies may lead to impressive remissions lasting for a long time in some patients. Regarding urological tumours, the anti-PD-1 antibody Nivolumab (Opdivo(®)) has been approved this year for advanced, previously treated renal cell carcinoma. In the United States, Atezolizumab (Tecentriq(®)) has been approved for metastatic urothelial carcinoma after platinum-based chemotherapy...

The paradigms for treating head and neck squamous cell carcinoma are changing as new subgroups are defined. The technical successes of improved radiation therapy are many; however, the success of novel combined therapies are few. With the emergence of human papillomavirus and the development of immunooncology agents, such as checkpoint inhibitors, are we ready to reevaluate how we use radiation and chemotherapy for locally advanced and metastatic disease-will we remain the fire or become the fire starter?

Lung cancer is a leading cause of cancer-related mortality worldwide, and is classically divided into two major histological subtypes: non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although NSCLC and SCLC are considered distinct entities with different genomic landscapes, emerging evidence highlights a convergence in therapeutically relevant targets for both histologies. In adenocarcinomas with defined alterations such as EGFR mutations and ALK translocations, targeted therapies are now first-line standard of care...

The fight against cancer has seen major breakthroughs in recent years. More than a decade ago, tyrosine kinase inhibitors targeting constitutively activated signaling cascades within the tumor inaugurated a new era of oncological therapy. Recently, immunotherapy with immune checkpoint inhibitors has started to revolutionize the treatment of several malignancies, most notably malignant melanoma, leading to the renaissance and the long-awaited breakthrough of immunooncology. This review provides an overview of the basis of immunotherapy from its initial concepts of anti-tumor immunity and cell-based therapy to the development of immune checkpoint inhibitors and discusses published studies and the perspectives of immunooncology for the treatment of endocrine malignancies...

Immunotherapeutic concepts in neurooncology have been developed for many decades but have mainly been hampered by poor definition of relevant antigens and selective measures to target the central nervous system. Independent of the recent remarkable successes in clinical immunooncology with checkpoint inhibitors and vaccines, immunotherapy of brain tumors in general and gliomas in particular has evolved with novel neurooncology-specific concepts over the past years providing new phase 1 approaches of individualized immunotherapy to first phase three clinical trials...

Cancer immunotherapy has been one of the dominant topics in oral presentations and abstracts during the 2015 annual meeting of the American Society of Clinical Oncology (ASCO). The renewed interest in immunotherapy is explained by the wide spectrum of activity, the durability of tumor responses and the rapid clinical development of immune-checkpoint targeted monoclonal antibodies. These new drugs are currently revolutionizing the field of oncology. Here we highlight what were to us the most important results announced during the annual meeting of ASCO held in Chicago, IL from May, 29th to June, 2nd 2015...

The last few years brought about a complete paradigm-shift in the field of melanoma therapy: eight new drugs, including three immunooncologic, four targeted and one oncolytic virus, became available in the daily practice. These new treatments provide a significantly increased overall survival potential for patients with metastatic melanoma. Choosing the optimal treatment for the individual patient, however, requires the careful evaluation of several patient- and drug-related factors, and poses a great challenge for the oncologists...

The introduction of molecular targeted agents has started to transform the treatment of metastatic renal cell carcinoma (mRCC), leading to a significant improvement of the prognosis of patients affected by that disease. However, treatment of metastatic disease still remains challenging as almost all patients will experience tumour progression and long-term survivors are very rare. This clearly warrants a continued search for improved treatment options. In recent years, the development of new substances and treatment approaches involving the targeted activation and modulation of the immune system have moved immunotherapy back into the focus of interest...

The classical model for identification and clinical development of anticancer agents was based on small molecules, which were often quite toxic. Early studies in small groups of patients would seek to identify a maximum tolerated dose and major dose-limiting toxicities. Tumor response (shrinkage) would be assessed after a minimum number of doses in phase II testing. The decision to take the drug into the randomized phase III clinical setting was usually based on the proportion and duration of objective tumor responses, along with overall survival compared with historical controls...

Fifty-two invasive ductal breast cancers were investigated histologically and immunohistologically to assess localization and composition of the lymphoreticular infiltrates. The tumour-infiltrating cells were mainly located in the intervening stroma, whereas tumour foci often exhibited lower numbers of lymphoreticular cells. Macrophages (Mono 1+ and KiM 6+) and helper/inducer cells bearing the T4 surface antigen (Leu-3a+) regularly constituted the majority of the tumour-infiltrating lymphoreticular cells. In more than 80% of cases large numbers of macrophages were found, and many T4 cells occurred in about 60%...